Abstract
Precise regulation of mtDNA transcription and oxidative phosphorylation (OXPHOS) is crucial for human health. As a component of mitochondrial contact site and cristae organizing system (MICOS), Mic60 plays a central role in mitochondrial morphology. However, it remains unclear whether Mic60 affects mitochondrial transcription. Here, we report that Mic60 interacts with mitochondrial transcription factors TFAM and TFB2M. Furthermore, we found that Mic60 knockdown compromises mitochondrial transcription and OXPHOS activities. Importantly, Mic60 deficiency decreased TFAM binding and mitochondrial RNA polymerase (POLRMT) recruitment to the mtDNA promoters. In addition, through mtDNA immunoprecipitation (mIP)-chromatin conformation capture (3C) assays, we found that Mic60 interacted with mtDNA and was involved in the architecture of mtDNA D-loop region. Taken together, our findings reveal a previously unrecognized important role of Mic60 in mtDNA transcription.
Highlights
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, P.R
We found that Mic[60] knockdown compromises mitochondrial transcription and oxidative phosphorylation (OXPHOS) activities
We report that Mic[60] interacts with mitochondrial transcription factors and Mic[60] deficiency decreases TFAM binding to mitochondrial DNA (mtDNA) promoters
Summary
As a component of mitochondrial contact site and cristae organizing system (MICOS), Mic[60] plays a central role in mitochondrial morphology It remains unclear whether Mic[60] affects mitochondrial transcription. Our findings reveal a previously unrecognized important role of Mic[60] in mtDNA transcription Mitochondria have their own genome comprised of mitochondrial DNA (mtDNA), which encodes 13 essential proteins within the oxidative phosphorylation (OXPHOS) complexes in vertebrates[1,2,3,4]. We report that Mic[60] interacts with mitochondrial transcription factors and Mic[60] deficiency decreases TFAM binding to mtDNA promoters. In this manner, suppression of Mic[60] compromises mitochondrial transcription and OXPHOS activities
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